We propose a series of investigations concerning the mechanisms through which self tolerance is maintained and autoimmunity prevented. Limiting dilution analysis of the autocytotoxic response will be utilized as a model for self tolerance in which the balance between autocytotoxic and autoregulatory cells can be demonstrated and manipulated. These two populations of cells will be studied utilizing limiting dilution analysis, T-cell cloning techniques, monoclonal antibodies, and cell separation techniques. Our goals are: to determine the phenotype of these populations and their precursors, identify their functional cell surface molecules, clone these cells, assess their growth requirements, characterize their target determinants, and analyze the interactions between these two populations. This work has potential relevance to autoimmune diseases, graft versus host disease, and tolerance to transplanted tissues.